Akt/GSK3β survival signaling is involved in acute brain injury after subarachnoid hemorrhage in rats
Akt/GSK3β survival signaling is involved in acute brain injury after subarachnoid hemorrhage in rats
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DOI：
10.1161/01.str.0000229888.55078.72
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发表时间：
2006-08-01
期刊：
影响因子：
8.3
通讯作者：
Chan, Pak H.
中科院分区：
文献类型：
--
作者：
Endo, Hidenori;Nito, Chikako;Chan, Pak H.
背景和目的：细胞凋亡与蛛网膜下腔出血（SAH）后急性脑损伤有关。Akt/糖原合成酶激酶-3 β（GSK 3 β）途径在多种细胞死亡刺激后的细胞死亡/存活途径中起重要作用。然而，它在SAH后急性脑损伤中的作用仍然未知。方法，我们使用了大鼠SAH血管内穿孔模型。通过Western印迹分析和免疫组织化学检测磷酸化Akt和磷酸化GSK 3 β表达。采用末端脱氧核苷酸转移酶介导的5 '-三磷酸尿苷-生物素缺口末端标记法（TUNEL）和细胞死亡实验检测细胞凋亡。我们给予LY 294002，以研究SAH. Results-Akt和GSK 3 β的磷酸化后，SAH. Results-Akt/GSK 3 β途径在磷脂酰肌醇3-激酶途径中的作用。在急性脑损伤最严重的大脑皮层中，在SAH后的早期阶段观察到这些蛋白的磷酸化。持续Akt磷酸化的皮质神经元在24小时不与TUNEL阳性细胞共定位。LY 294002减少Akt和GSK 3 β磷酸化，增加SAH. Conclusions后的脑损伤，本研究表明，Akt/GSK 3 β通路可能参与SAH后急性脑损伤的神经元存活。
Background and Purpose-Apoptotic cell death is associated with acute brain injury after subarachnoid hemorrhage (SAH). The Akt/glycogen synthase kinase-3 beta (GSK3 beta) pathway plays an important role in the cell death/survival pathway after a variety of cell death stimuli. However, its role in acute brain injury after SAH remains unknown.Methods-We used an endovascular perforation model of SAH in rats. Phospho-Akt and phospho-GSK3 beta expression was examined by Western blot analysis and immunohistochemistry. Terminal deoxynucleotidyl transferase-mediated uridine 5'-triphosphate-biotin nick end-labeling (TUNEL) and a cell death assay were used for detection of apoptosis. We administered LY294002 to examine the role of the Akt/GSK3 beta pathway in the phosphoinositide 3-kinase pathway after SAH.Results-Phosphorylation of Akt and GSK3 beta was accelerated after SAH. In the cerebral cortex, where acute brain injury was the most severe, phosphorylation of these proteins was observed in the early phase after SAH. Cortical neurons with continuous Akt phosphorylation did not colocalize with TUNEL-positive cells at 24 hours. LY294002 reduced Akt and GSK3 beta phosphorylation and increased brain injury after SAH.Conclusions-The present study suggests that the Akt/GSK3 beta pathway might be involved in neuronal survival in acute brain injury after SAH.